Safety profile of first-line targeted therapies in elderly and/or comorbid chronic lymphocytic leukaemia patients (unfit subpopulation). A systematic review and network meta-analysis
Anita Stożek-Tutro, Monika Reczek, Paweł Kawalec
Abstract
This systematic literature review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1–5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1–5. The use of Bruton’s tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities. • Targeted therapies improved chronic lymphocytic leukemia prognosis. • The relative efficacy of targeted therapies is established but not their safety. • Systematic review with network meta-analysis conducted to assess relative safety. • Distinct relative safety profiles identified for each targeted therapy. • Targeted drug monotherapy appears better tolerated than combination therapy.